The main objective of this proposal is to test the hypothesis that serotonin (5-HT) has a role embryologically in closure of the caudal portion of the neural tube. This hypothesis is based upon strong suggestive evidence provided by morphologic and preliminary pharmacologic investigations. Because of the weight of the morphologic evidence as well as the potential clinical relevance of such studies, it is suggested that further pharmacologic and teratologic experimentation is warranted to clarify if 5-HT is indeed required for some aspect of caudal neural tube closure. It is proposed that this question be resolved by 3 successive investigations in the chick embryo. 1) Neuropharmacologic agents that affect adult neuronal 5-HT systems will be evaluated immunocytochemically for their action on embryonic 5-HT systems. 2) An antiserum to 5-HT and those neuropharmacologic agents demonstrated to affect embryonic 5-HT systems will be tested for their teratologic potential in long and short-term in vitro culture experiments. 3) To ascertain if the teratologic effects produced by the antiserum or drugs is related to their interference of 5-HT's role in neural tube closure, attempts will be made to reverse these effects and reduce the frequency of neural tube defects observed in the preceding study. Besides providing information basic to the fields of developmental neurobiology and embryology, these studies may be significant to our understanding of the etiology of neural tube defects (particularly spina bifida) and may lead to the prevention of these commonly occurring congenital malformations.